In industrial scale fermentation processes (50-500+ m3), mixing of, for example, the glucose feed can take up to several minutes. Feeding usually happens locally, whereas glucose is consumed throughout the fermentor. This means that the amount of glucose near the feed may be very different than far away from it: gradients in concentration may occur. Fermentations are conducted using micro-organisms such as yeast or fungi, which move through the fermentor due to mixing. Taking their perspective, the observed glucose concentration varies in time, depending on where they are in the fermentor.

These changes in time may influence the metabolism of the micro-organisms, which may impact the productivity of large fermentors, often negatively. It is therefore important that these glucose fluctuations are included when testing fermentation performance in the laboratory. If not, the performance may be evaluated under the wrong conditions, and if genetic modification of the micro-organism is conducted, it may be optimized for the wrong conditions. However, how big these glucose fluctuations are in industrial fermentors, is typically unknown.

In my thesis work, computational fluid dynamics, describing mixing in industrial fermentors, was combined with models that capture the response of the metabolism of microbes. With this, it is possible to estimate how microbes experience glucose fluctuations in industrial fermentors, as well as how the process performance responds to these fluctuations. For example, it was possible to estimate the loss of productivity for an industrial penicillin process compared to a lab-scale process. Furthermore, these simulations were used to design laboratory scale experiments where the glucose feed is deliberately varied, to better reflect industrial conditions during lab-scale evaluation. To summarize: to properly assess large-scale fermentation processes, they should be evaluated through the organism’s eyes.

More information?

For access to theses by the PhD students you can have a look in TU Delft Repository, the digital storage of publications of TU Delft. Theses will be available within a few weeks after the actual thesis defence.